The purpose of this study is to compare the effect of NKTR-118 with placebo in the treatment of opioid-induced constipation (OIC) in patients with cancer-related pain, including those patients that have inadequate response to laxative therapy (LIR).

The study consists of 2 parts; A initial 4-week treatment period (part A) and then a 12 week extension with active treatment (part B).

Response to study drug, defined as having at least 3 Rescue-free bowel movements (RFBMs) per week during the 4-week treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks. [ Time Frame: Will be collected daily through the 4-week treatment period. ] [ Designated as safety issue: No ]

Response (responder/non-responder) to study drug, where a responder is defined as having at least 3 Rescue-free bowel movements (RFBMs) per week during the 4-week treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks.

Secondary Outcome Measures:

Part A and Part B: Change from baseline in RFBMs/week [ Time Frame: Will be collected daily through the 4-week treatment period as well as the 12 week extension ] [ Designated as safety issue: No ]

Part A and Part B: mean number of days per week with at least 1 RFBM. [ Time Frame: Will be collected daily through the 4-week treatment period as well as athe 12 week extension ] [ Designated as safety issue: No ]

Part A: Time (in hours) to first post-dose RFBM [ Time Frame: Will be collected daily through the 4-week treatment period part A only. ] [ Designated as safety issue: No ]

Part A: Change from baseline in the degree of straining associated with RFBMs during the 4-week placebo-controlled treatment period. [ Time Frame: Will be collected daily through the 4-week treatment period part A only. ] [ Designated as safety issue: No ]

Part A: Change from baseline in stool consistency (BSS) during the 4-week placebo-controlled treatment period. [ Time Frame: Will be collected daily through the 4-week treatment period .part A only. ] [ Designated as safety issue: No ]

Part A: Percentage of days with complete evacuation during the 4-week placebo-controlled treatment period. [ Time Frame: Will be collected daily through the 4-week treatment period part A only. ] [ Designated as safety issue: No ]

Part A and B: Change from baseline in Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) total score and each domain score for Weeks 2 and 4. [ Time Frame: Part A: Will be evaluated at Visits 3, 5 and 6. Part B: will be evaluated at Visits 4 and 6. ] [ Designated as safety issue: No ]

Self-reported active symptoms of OIC at screening (<3 RFBMs/week and experiencing >1 reported symptom of hard/lumpy stools, straining, or sensation of incomplete evacuation/anorectal obstruction in at least 25% of BMs over the previous 4 weeks); and Documented confirmed OIC (<3 RFBMs/week on average aver the 2-week OIC confirmation period.

Receiving a stable maintenance opioid regimen consisting of a total daily dose of >30 mg of oral morphine, or equianalgesic amount(s) of 1 or more opioid therapies for a minimum of 4 weeks prior to screening for cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression.

Exclusion Criteria:

Patients receiving Opioid regimen for treatment of pain other than related to cancer.

Patients with cancer-related pain due to ovarian cancer, leukaemia, or lymphoma are excluded. Patients with multiple myeloma will be allowed.

Patients requiring radiation therapy between the diaphragm and pelvis 4 weeks prior to Visit 1 (screening) and/or during Part A of the study are excluded. Any patients with suspected clinically relevant radiation-induced injury of small or large intestine are excluded.

Pregnancy or lactation.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01384292